IGF2 confers genetic susceptibility to the risk of ischemic stroke with differential mRNA expression in leukocytes

Background Insulin-like growth factor 2 ( IGF2 ), has been proven to be involved in vascular health, neuroprotection, and inflammation modulation which are relevant to the mechanism of ischemic stroke (IS). This study aimed to investigate the effect of IGF2 variants and mRNA expression on IS. Method Three tag SNPs rs3741211, rs10770125, rs2585 were genotyped in a case-control study and two cohorts to evaluate the genetic effect on the incidence and prognosis of IS. IGF2 mRNA expression in leukocytes was measured. Results In the case-control study, the variations of rs3741211 and rs2585 were significantly associated with the increased risk of IS and odds ratios ( OR s) of dominant model were 1.130 and 1.151. The association of rs3741211 and IS remains significant in hypertension group (adjusted OR : 1.268; P  = 0.003) with additive interactions of hypertension ( P  < 0.05). IGF2 mRNA expression of IS cases were significantly lower than controls (fold change = 0.740, P  = 0.002) and there was a nonlinear relationship between IGF2 mRNA expression of IS ( P  < 0.05). Furthermore, the variations of rs3741211, rs10770125, and rs2585 are significantly associated with increased expression levels of IGF2 mRNA ( P  < 0.05). Additionally, a negative correlation was observed between IGF2 mRNA level and both National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores in IS patients after discharge ( P  < 0.05). Conclusions The study reveals that IGF2 gene is associated with the susceptibility of IS and rs3741211, rs10770125, and rs2585 may affect the expression levels of IGF2 mRNA. Furthermore, IGF2 mRNA level was downregulated in IS patients and negatively correlate with poor prognosis.